Examination of the gene therapy for OME using Decoy oligo.

使用诱饵寡核苷酸检查 OME 基因治疗。

• 批准号: 15591823
• 负责人: MATSUNE Shoji
• 金额: $ 2.18万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591823/
• 关键词: NF-κB; Decoy Oligo; gene therapy; OME; sinusitis; NF-κBデコイ; センダイウイルス; アデノイド線維芽細胞; デコイ; マウス; 炎症性サイトカイン; NF-kB

TNF-a induced or upregulated IL-8 production in adenoidal fibroblasts. IL-8 level in epipharyngeal effusion and the compliance of tympanic membrane was showed clinically to be correlated in OME, suggesting that I L-8 production from adenoidal fibroblasts is one of the important causative factors of OME. Additionally, VCAM-1 was induced by the stimulation of TNF-a and/or IL-4 in nasal fibroblasts.Translocation of NF-κB is the essential step both in IL-8 production in adenoidal fibroblasts and VCAM-1 production from nasal fibroblasts.Based on these data, NF-κ B is the key factor and the regulation of this step seems to be a new strategy to treat OME and C S.In this project, NF-κB Decoy oligo was expected to suppress the activation of NF-IC B translocation. We applied the liposome method and sendai virus vector to transfect NF-κ B Decoy oligo to cultured fibroblast. However, the transfection was not successful and we could not go to the step of the application of this strategy to the OME mouse model.

TNF-α诱导或上调腺样体成纤维细胞中IL-8的产生。分泌性中耳炎患者咽鼓管渗出液中IL-8水平与鼓膜顺应性相关，提示增殖体成纤维细胞分泌IL-8是分泌性中耳炎的重要致病因素之一。另外，鼻成纤维细胞中的VCAM-1可通过TNF-α和/或IL-4的刺激来诱导。NF-κB的易位是腺样体成纤维细胞产生IL-8和鼻成纤维细胞产生VCAM-1的关键步骤。基于这些数据，NF-κ B是关键因素，调节这一步骤似乎是治疗OME和CS的新策略。NF-κB诱骗寡核苷酸有望抑制NF-κ IC B易位的激活。采用脂质体法和仙台病毒载体将NF-κ B Decoy oligo转染到体外培养的成纤维细胞中。然而，转染并不成功，我们无法进行将该策略应用于OME小鼠模型的步骤。

项目成果

TNF-a upregulates VCAM-1 and NF-κ B in fibroblasts form nasal polyps.

TNF-a 上调鼻息肉成纤维细胞中的 VCAM-1 和 NF-κ B。

• 期刊: Auris Nasus Larynx (in press)
• 作者: J.Ohori;M.Ushikai;Dong Sun;K.Nishimoto;Y.Sagara;T.Fukuiwa;S.Matsune;Y.Kurono
• 通讯作者: Y.Kurono

TNF-α and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion

TNF-α 和内毒素以协同方式增加培养的人鼻成纤维细胞缺氧诱导的 VEGF 产生

• 发表时间: 2005
• 期刊: Auris Nasus Larynx 32(3)
• 作者: Fukuyama S;et al.;黒野祐一;Dung Sun
• 通讯作者: Dung Sun

The role of nuclear factor-κB in interleukin-8 expression by human adenoidal fibroblasts.

核因子-κB 在人腺样成纤维细胞表达白细胞介素 8 中的作用。

• 发表时间: 2003
• 期刊: Laryngoscope 113(8)
• 作者: Takaki M.;Ushikai M.;Deguchi K.;Nishmoto K.;Matsune S.;Kurono Y.
• 通讯作者: Kurono Y.

AOM, OME and Adenoid, Tonsil.

AOM、OME 和腺样体、扁桃体。

• 发表时间: 2004
• 期刊: JOHNS 20(5)
• 作者: M.Ushikai;T.Hayashi;Y.Sagara;Y.Kurono
• 通讯作者: Y.Kurono

The role of nuclear factor-κ B in interleukin-8 expression by human adenoidal fibroblasts.

核因子-κ B 在人腺样成纤维细胞表达白细胞介素 8 中的作用。

• 发表时间: 2003
• 期刊: Laryngoscope 113(8)
• 作者: M.Ushikai;T.Hayashi;Y.Sagara;Y.Kurono;Takaki M. et al.
• 通讯作者: Takaki M. et al.